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1.
Infection ; 47(5): 847-852, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31190299

RESUMO

PURPOSE: Due to early antenatal screening and treatment, HIV mother-to-child transmission (MTCT) rarely occurs in Germany. The study aimed to investigate the impact on prevalence of HIV infection in the antenatal population and the incidence of late-presenting HIV-infected mothers attributable to increased numbers of refugees. METHODS: Retrospective analysis and comparison were performed for all deliveries in HIV-infected pregnant women presenting to medical care in Munich (southern Germany) and Hamburg (northern Germany) covering two time periods, A (2010-2012) and B (2013-2015). RESULTS: In Munich, deliveries in HIV-infected pregnant women increased 1.6-fold from period A (n = 50) to B (n = 79) with late-presenting cases rising significantly from 2% (1/50) in period A to 13% (10/79) in B. In contrast, late-presenting cases in Hamburg decreased from 14% (14/100) in period A to 7% (7/107) in B, while the total number of HIV-infected women giving birth remained stable. From 2010 to 2015, one late-presenting pregnant woman transmitted HIV in Munich by presumed in utero mode of infection (case reviewed here), while no MTCT occurred in Hamburg. CONCLUSIONS: HIV infections diagnosed late in pregnancy and leading to delayed ART initiation are rising in Munich compared to Hamburg. Antenatal care of HIV-infected pregnant women in Munich appears to have been more affected by the recent refugee influx than Hamburg. Our study highlights the importance of screening all pregnant women for HIV early in pregnancy and providing timely health care access for pregnant refugees and asylum seekers to effectively prevent MTCT in Germany.


Assuntos
Infecções por HIV/epidemiologia , Transmissão Vertical de Doenças Infecciosas/estatística & dados numéricos , Complicações Infecciosas na Gravidez/epidemiologia , Complicações Infecciosas na Gravidez/virologia , Refugiados , Adulto , Fármacos Anti-HIV/uso terapêutico , Feminino , Geografia , Alemanha/epidemiologia , Infecções por HIV/diagnóstico , Infecções por HIV/tratamento farmacológico , HIV-1 , Acessibilidade aos Serviços de Saúde , Humanos , Gravidez , Prevalência , Estudos Retrospectivos , Tempo para o Tratamento , Adulto Jovem
2.
Eur J Pediatr ; 175(6): 793-8, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-26898704

RESUMO

UNLABELLED: Red blood cell transfusion can improve but also might temporarily reduce the microcirculation. The buccal microcirculation was visualized and total vessel density (TVD) determined with sidestream dark field imaging in 19 pediatric anemic (Hb 7.2 g/dL, 95 % CI 6.5-7.9) oncology or hematology patients receiving red blood cell transfusions (Tx) and in 18 age-matched healthy non-anemic controls. After transfusion, Hb (8.0 g/dL, 95 % CI 7.3-8.6) and TVD increased (14.7 ± 1.7 versus 16.6 ± 2.0 mm/mm(2)) significantly with a concomitant decrease in RBC velocity in medium-sized vessels (pre-Tx 711 ± 199 versus post-Tx 627 ± 163 µm/s). Compared to the controls, pre-Tx TVD (17.5 ± 1.3 mm/mm(2)) was lower and RBC velocity (476 ± 77 µm/s) was significantly higher. After transfusion, TVD and RBC velocity remained significantly lower and higher, respectively. In a subgroup, analysis of the transfused children with infection of TVD at baseline was lower with a larger increase after transfusion compared to anemic children without infection (ΔTVD 3.4 ± 2.6 versus ΔTVD 1.3 ± 1.5 mm/mm(2)). CONCLUSION: With the rise of hemoglobin after transfusion, significant improvements of tissue perfusion were demonstrated but differences to non-anemic controls persisted. In particular, the microcirculation of anemic oncology patients with infection improved after transfusion. WHAT IS KNOWN: • Transfusions can improve but also temporarily reduce the microcirculation. • In neonates, transfusion significantly increases total vessel density. What is New: • Pretransfusion, the microcirculation of the anemic children differed significantly from the controls. • After transfusion, the microcirculation improved but still differed from the controls. • These changes were most profound in anemic patients with concurrent infection, therefore transfusion threshholds might need to be higher.


Assuntos
Anemia/sangue , Transfusão de Eritrócitos , Microcirculação , Mucosa Bucal/irrigação sanguínea , Adolescente , Anemia/diagnóstico por imagem , Anemia/terapia , Estudos de Casos e Controles , Criança , Índices de Eritrócitos , Feminino , Humanos , Masculino , Estudos Prospectivos
3.
Blood ; 121(21): e118-28, 2013 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-23525796

RESUMO

In adult mammals, leukocyte recruitment follows a well-defined cascade of adhesion events enabling leukocytes to leave the circulatory system and transmigrate into tissue. Currently, it is unclear whether leukocyte recruitment proceeds in a similar fashion during fetal development. Considering the fact that the incidence of neonatal sepsis increases dramatically with decreasing gestational age in humans, we hypothesized that leukocyte recruitment may be acquired only late during fetal ontogeny. To test this, we developed a fetal intravital microscopy model in pregnant mice and, using LysEGFP (neutrophil reporter) mice, investigated leukocyte recruitment during fetal development. We show that fetal blood neutrophils acquire the ability to roll and adhere on inflamed yolk sac vessels during late fetal development, whereas at earlier embryonic stages (before day E15), rolling and adhesion were essentially absent. Accordingly, flow chamber experiments showed that fetal EGFP(+) blood cells underwent efficient adhesion only when they were harvested on or after E15. Fluorescence-activated cell sorter analysis on EGFP(+) fetal blood cells revealed that surface expression of CXCR2 and less pronounced P-selectin glycoprotein ligand-1 (PSGL-1) begin to increase only late in fetal life. Taken together, our findings demonstrate that inflammation-induced leukocyte recruitment is ontogenetically regulated and enables efficient neutrophil trafficking only during late fetal life.


Assuntos
Movimento Celular/imunologia , Sistema Imunitário/embriologia , Leucócitos/citologia , Microvasos/embriologia , Saco Vitelino/embriologia , Animais , Adesão Celular/imunologia , Eritroblastos/citologia , Feminino , Sangue Fetal/citologia , Proteínas de Fluorescência Verde/metabolismo , Sistema Imunitário/citologia , Migração e Rolagem de Leucócitos/imunologia , Leucócitos/metabolismo , Glicoproteínas de Membrana/metabolismo , Camundongos , Microvasos/citologia , Microvasos/imunologia , Neutrófilos/citologia , Neutrófilos/metabolismo , Selectina-P/metabolismo , Gravidez , Receptores de Interleucina-8B/metabolismo , Saco Vitelino/irrigação sanguínea , Saco Vitelino/citologia
4.
BMC Med Educ ; 15: 94, 2015 Jun 02.
Artigo em Inglês | MEDLINE | ID: mdl-26032301

RESUMO

BACKGROUND: Pathology is a discipline that provides the basis of the understanding of disease in medicine. The past decades have seen a decline in the emphasis laid on pathology teaching in medical schools and outdated pathology curricula have worsened the situation. Student opinions and thoughts are central to the questions of whether and how such curricula should be modernized. METHODS: A survey was conducted among 1018 German medical students regarding their preferences in pathology teaching modalities and their satisfaction with lecture-based courses. A qualitative analysis was performed comparing a recently modernized pathology curriculum with a traditional lecture-based curriculum. The differences in modalities of teaching used were investigated. RESULTS: Student satisfaction with the lecture-based curriculum positively correlated with student grades (spearman's correlation coefficient 0.24). Additionally, students with lower grades supported changing the curriculum (spearman's correlation coefficient 0.47). The majority supported virtual microscopy, autopsies, seminars and podcasts as preferred didactic methods. CONCLUSIONS: The data supports the implementation of a pathology curriculum where tutorials, autopsies and supplementary computer-based learning tools play important roles.


Assuntos
Atitude do Pessoal de Saúde , Comportamento de Escolha , Currículo , Educação Médica , Patologia/educação , Estudantes de Medicina/psicologia , Adulto , Instrução por Computador , Avaliação Educacional , Feminino , Alemanha , Humanos , Masculino , Modelos Educacionais , Inquéritos e Questionários , Adulto Jovem
5.
J Pediatr ; 164(3): 584-9.e1, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24367980

RESUMO

OBJECTIVE: To evaluate the microcirculation of children with type 1 diabetes mellitus who demonstrate no clinical signs of diabetic microangiopathy for the presence of microvascular alterations and glycocalyx perturbation. STUDY DESIGN: Images of sublingual vessels were obtained in 14 children with diabetes (ages 12.8 ± 2.8 years, diabetes duration 6.7 ± 4.3 years) and 14 control patients (ages 11.8 ± 2.8 years) by the use of sidestream dark field imaging and analyzed for total vessel density, vessel surface coverage, vessel diameter distribution, mean flow index, and glycocalyx thickness. Wilcoxon rank sum test and Pearson correlation were used for statistical analysis. RESULTS: We observed profound microcirculatory changes in children with diabetes compared with control patients, with a significant reduction of glycocalyx thickness (0.38 µm vs 0.60 µm; P = .013), which was inversely correlated with blood glucose levels (r = -0.55; P = .003). Furthermore, the percentage of large vessels (>20 µm diameter) was significantly increased (11% vs 6%; P = .023) at the expense of capillaries (<10 µm diameter) with consequent increase in total vessel surface coverage (30% vs 26.0%; P = .041). No differences were seen in total vessel density and mean flow index. CONCLUSIONS: Microvascular alterations, including changes in microvessel distribution and loss of the glycocalyx, can be detected in children with type 1 diabetes mellitus before clinically apparent vascular complications. Our results disclose the glycocalyx as a possible monitoring measurement for earlier detection of diabetic microangiopathy and may provide a basis for new therapeutic strategies aiming at protection or restoration of the glycocalyx.


Assuntos
Diabetes Mellitus Tipo 1/patologia , Diabetes Mellitus Tipo 1/fisiopatologia , Glicocálix/ultraestrutura , Microcirculação/fisiologia , Microvasos/ultraestrutura , Adolescente , Glicemia/análise , Capilares/ultraestrutura , Estudos de Casos e Controles , Criança , Endotélio Vascular/ultraestrutura , Feminino , Humanos , Masculino , Soalho Bucal/irrigação sanguínea
6.
Eur J Pediatr ; 173(11): 1519-25, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-24942237

RESUMO

UNLABELLED: Neonatal blue light phototherapy (NBLP) is an effective treatment for hyperbilirubinaemia. Concerning the influence on melanocytic nevi, conflicting studies have been published. To assess the role of NBLP according to the incidence of melanocytic nevi in preschool children, a cohort of 104 5- to 6-year-old children were included. The case group consisted of 52 NBLP-exposed children, while the control group (n = 52) never had NBLP and was matched regarding age, gender, gestational age and skin phototype. Six dizygotic twins were included with one twin having received NBLP, respectively. The following parameters were recorded: nevi count, presence of freckles, café-au-lait macules, skin phototype and previous history of sun exposure. There was no significant association between nevi count and exposure to NBLP (median nevi count 17.0 compared to 18.5 in controls). No significant difference was also found in the dizygotic twin pairs with a median nevi count of 10.0 (with NBLP) compared to 14.5 (without NBLP). However, a significantly higher prevalence of café-au-lait macules was found in children with NBLP (mean count 0.5) than in children without NBLP (mean count 0.2; p = 0.001). Significant predictors for the number of melanocytic nevi included skin phototype, sun exposure and vacations in the South. CONCLUSION: In this study, NBLP had no significant influence on the development of melanocytic nevi, but on café-au-lait macules which was a new finding. Differences with comparable studies regarding age, differentiation between nevi and other pigmented lesions as well as dose and type of NBLP need to be taken into account for further investigations.


Assuntos
Manchas Café com Leite/etiologia , Fototerapia/efeitos adversos , Neoplasias Cutâneas/etiologia , Manchas Café com Leite/epidemiologia , Estudos de Casos e Controles , Criança , Pré-Escolar , Feminino , Alemanha , Humanos , Hiperbilirrubinemia/terapia , Recém-Nascido , Masculino , Nevo Pigmentado/epidemiologia , Nevo Pigmentado/etiologia , Prevalência , Estudos Retrospectivos , Pele/patologia , Neoplasias Cutâneas/epidemiologia , Inquéritos e Questionários , Gêmeos Dizigóticos
7.
Clin Teach ; 21(4): e13749, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38433499

RESUMO

OBJECTIVE: The accurate documentation of a medical history interview is an important goal in medical education. As students' documentation of medical history interviews is mostly decentralised on the wards, a systematic assessment of documentation quality is missing. We therefore evaluated the extent of details missed in students' medical history reports in a standardised setting. METHODS: In this prospective, observational study, 123 of 380 students (32.4%) participated in an Objective Structured Clinical Examination (OSCE) regarding history taking and documentation. Based on the interviews and nine deductively selected main categories, a categorical system was established using a summarising qualitative content analysis. The items in the transcripts (defined as ground truth) and in students' reports were labelled and assigned to the correct subcategory. The ground truth and students' reports were compared to quantify students' documentation completeness. RESULTS: Next to the nine deductively selected main categories, 61 subcategories were defined. A total of 8943 items were labelled in the 123 interview transcripts (ground truth), compared with 5870 items labelled in students' reports (65.6% completeness of students' reports compared with ground truth). The main category personal details overlapped with 94.2% between students' report and ground truth in contrast to the main category with the highest discrepancy, allergy, with 41.1% overlap. Pertinent negative items and non-numerical quantifications were often missed. CONCLUSIONS: Medical students show incomplete documentation of medical history interviews. Therefore, accurate documentation should be taught as an important goal in medical education.


Assuntos
Documentação , Anamnese , Estudantes de Medicina , Humanos , Estudantes de Medicina/psicologia , Anamnese/normas , Documentação/normas , Estudos Prospectivos , Masculino , Feminino , Educação de Graduação em Medicina , Competência Clínica , Entrevistas como Assunto
8.
Pediatr Res ; 74(2): 186-90, 2013 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-23802219

RESUMO

BACKGROUND: Hypotension remains a common complication in preterm infants and is associated with high neonatal morbidity and mortality. The underlying mechanisms are still not fully understood. We studied the microcirculation in extremely low birth weight infants to understand the relationship between blood pressure and skin perfusion. METHODS: In 21 patients (gestational age <30 wk, birth weight <1,225 g), functional vessel density (FVD) and diameter distribution were obtained prospectively by side stream dark-field imaging at the right arm in the first 48 h after birth. Infants with blood pressure below gestational age and receiving catecholamines were defined as hypotensive as compared with the remaining normotensive control group. RESULTS: In the first 6 h after birth, FVD was significantly higher in the hypotensive group than in the control group. After 12 h, there were no significant differences in either blood pressure or FVD between the two groups. FVD did not change significantly during the observation period in either group. CONCLUSION: Hypotensive infants have a higher FVD, possibly due to loss of microvascular tone leading to vasodilation and flow redistribution. However, the link between blood pressure and perfusion remains unclear, and no definitive correlation could be found.


Assuntos
Hipotensão/fisiopatologia , Recém-Nascido de Peso Extremamente Baixo ao Nascer/fisiologia , Recém-Nascido Prematuro/fisiologia , Microcirculação/fisiologia , Pressão Sanguínea/fisiologia , Alemanha , Humanos , Recém-Nascido , Estudos Prospectivos , Pele/irrigação sanguínea
9.
Clin Hemorheol Microcirc ; 83(3): 217-229, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36502307

RESUMO

BACKGROUND: Monitoring of the macrocirculation during surgery provides limited information on the quality of organ perfusion. OBJECTIVE: We investigated the feasibility of perioperative microcirculatory measurements in children. METHODS: Sublingual microvessels were visualized by handheld videomicroscopy in 11 children (19 mo - 10 yrs) undergoing surgery > 120 min at four time points: T0) after induction of anesthesia; T1) before end of anesthesia, T2) 6 h post surgery and T3) 24 h post surgery. RESULTS: Measurements were feasible in all children at T0 and T1. At T2 and T3, imaging was restricted to 6 and 4 infants, respectively, due to respiratory compromise and missing cooperation. The capillary density was reduced at T1 compared to T0 (8.1 mm/mm2 [4.0-17.0] vs. 10.6 mm/mm2 [5.1-19.3]; p = 0.01), and inversely related to norepinephrine dose (Pearson r = -0.65; p = 0.04). Microvascular flow and serum glycocalyx makers Syndecan-1 and Hyaluronan increased significantly from T0 to T1. CONCLUSION: Perioperative microcirculatory monitoring in children requires a high amount of personal and logistic resources still limiting its routine use. Major surgery is associated with microvascular alterations and glycocalyx perturbation. The possible consequences on patient outcome need further evaluation. Efforts should concentrate on the development of next generation devices designed to facilitate microcirculatory monitoring in children.


Assuntos
Cirurgia Torácica , Humanos , Criança , Microcirculação , Projetos Piloto , Glicocálix , Abdome
11.
GMS J Med Educ ; 39(3): Doc34, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36119150

RESUMO

Objective: Obtaining a systematic medical history (MH) from a patient is a core competency in medical education and plays a vital role in the diagnosis of diseases. At the Faculty of Medicine at LMU Munich, students have their first course in MH taking during their second year. Due to the COVID-19 pandemic, the traditional bedside MH taking course had to be transformed into an online course (OC). Our objectives were to implement an online MH taking course, to evaluate its feasibility and to compare the evaluation results to a historic cohort that had undertaken the traditional bedside teaching course (BTC). Methods: 874 second-year students participated in the OC (BTC=827). After teaching the theoretical background via asynchronous online lectures, students participated in a practical exercise with fellow students using the video communication platform Zoom where they were able to practice taking a MH on the basis of fictitious, text-based patient cases. Students were then asked to evaluate the course through a standardized online survey with 31 questions on teaching quality and self-perceived learning success, which had also been used in previous years. The survey results were compared to the results of the historic cohort using the Mann-Whitney U test. Results: A total of n=162 students (18.5%) evaluated the OC. In the historic cohort, n=252 (30.5%) completed the survey. 85.3% of the OC respondents thought that the atmosphere during the practical exercise was productive and 83.0% greatly appreciated the flexibility in terms of time management. Moreover, they appreciated the online resources as well as having the opportunity to undertake a MH taking course during the COVID-19 pandemic. 27.7% of the respondents thought that traditional BTCs should be supplemented through more online activities in the future. With respect to the ability of independently taking a MH upon completion of the course, the OC was rated significantly lower relative to the BTC (mean OC=2.4, SD=±1.1 vs. mean BTC=1.9, SD=±1.1 (1=strongly agree; 5=strongly disagree); p<0.0001). Conclusion: OCs are a feasible format and seem to convey the theory and practical implementation in a peer-exercise format of MH taking to medical students. The theoretical background can be acquired with great flexibility. Nevertheless, the students' self-appraisal suggested that the traditional teaching format was more effective at teaching MH taking skills. Thus, we propose a blended learning concept, combining elements of both formats. In this context, we suggest prospective, randomized trials to evaluate blended learning approaches.


Assuntos
COVID-19 , COVID-19/epidemiologia , Humanos , Aprendizagem , Anamnese , Pandemias , Estudos Prospectivos
12.
Children (Basel) ; 9(9)2022 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-36138599

RESUMO

The factors influencing weaning of preterm infants from noninvasive ventilation (NIV) are poorly defined and the weaning decisions are often driven by subjective judgement rather than objective measures. To standardize quantification of respiratory effort, the Silverman-Andersen Score (SAS) was included in our nursing routine. We investigated the factors that steer the weaning process and whether the inclusion of the SAS would lead to more stringent weaning. Following SAS implementation, we prospectively evaluated 33 neonates born ≤ 32 + 0 weeks gestational age. Age-, weight- and sex-matched infants born before routine SAS evaluation served as historic control. In 173 of 575 patient days, NIV was not weaned despite little respiratory distress (SAS ≤ 2), mainly due to bradycardias (60% of days without weaning), occurring alone (40%) or in combination with other factors such as apnea/desaturations. In addition, "soft factors" that are harder to grasp impact on weaning decisions, whereas the SAS overall played a minor role. Consequently, ventilation times did not differ between the groups. In conclusion, NIV weaning is influenced by various factors that override the absence of respiratory distress limiting the predictive value of the SAS. An awareness of the factors that influence weaning decisions is important as prolonged use of NIV has been associated with adverse outcome. Guidelines are necessary to standardize NIV weaning practice.

13.
PLoS Genet ; 4(12): e1000289, 2008 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-19057668

RESUMO

Kindler Syndrome (KS), characterized by transient skin blistering followed by abnormal pigmentation, skin atrophy, and skin cancer, is caused by mutations in the FERMT1 gene. Although a few KS patients have been reported to also develop ulcerative colitis (UC), a causal link to the FERMT1 gene mutation is unknown. The FERMT1 gene product belongs to a family of focal adhesion proteins (Kindlin-1, -2, -3) that bind several beta integrin cytoplasmic domains. Here, we show that deleting Kindlin-1 in mice gives rise to skin atrophy and an intestinal epithelial dysfunction with similarities to human UC. This intestinal dysfunction results in perinatal lethality and is triggered by defective intestinal epithelial cell integrin activation, leading to detachment of this barrier followed by a destructive inflammatory response.


Assuntos
Proteínas de Transporte/genética , Epitélio/fisiopatologia , Técnicas de Inativação de Genes , Intestinos/fisiopatologia , Dermatopatias Genéticas/metabolismo , Dermatopatias Genéticas/mortalidade , Pele/patologia , Animais , Animais Recém-Nascidos , Atrofia/metabolismo , Atrofia/mortalidade , Atrofia/fisiopatologia , Proteínas de Transporte/metabolismo , Adesão Celular , Linhagem Celular , Colite Ulcerativa/metabolismo , Colite Ulcerativa/mortalidade , Colite Ulcerativa/patologia , Colite Ulcerativa/fisiopatologia , Epitélio/metabolismo , Epitélio/patologia , Humanos , Mucosa Intestinal/metabolismo , Intestinos/patologia , Camundongos , Camundongos Knockout , Pele/metabolismo , Pele/fisiopatologia , Dermatopatias Genéticas/patologia , Dermatopatias Genéticas/fisiopatologia
14.
Front Cell Dev Biol ; 9: 733557, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34540845

RESUMO

The endothelial glycocalyx (EG) as part of the endothelial surface layer (ESL) is an important regulator of vascular function and homeostasis, including permeability, vascular tone, leukocyte recruitment and coagulation. Located at the interface between the endothelium and the blood stream, this highly fragile structure is prone to many disruptive factors such as inflammation and oxidative stress. Shedding of the EG has been described in various acute and chronic diseases characterized by endothelial dysfunction and angiopathy, such as sepsis, trauma, diabetes and cardiovascular disease. Circulating EG components including syndecan-1, hyaluronan and heparan sulfate are being evaluated in animal and clinical studies as diagnostic and prognostic markers in several pathologies, and advances in microscopic techniques have enabled in vivo assessment of the EG. While research regarding the EG in adult physiology and pathology has greatly advanced throughout the last decades, our knowledge of the development of the glycocalyx and its involvement in pathological conditions in the pediatric population is limited. Current evidence suggests that the EG is present early during fetal development and plays a critical role in vessel formation and maturation. Like in adults, EG shedding has been demonstrated in acute inflammatory conditions in infants and children and chronic diseases with childhood-onset. However, the underlying mechanisms and their contribution to disease manifestation and progression still need to be established. In the future, the glycocalyx might serve as a marker to identify pediatric patients at risk for vascular sequelae and as a potential target for early interventions.

15.
Sci Rep ; 11(1): 3133, 2021 02 04.
Artigo em Inglês | MEDLINE | ID: mdl-33542284

RESUMO

Prematurity predisposes to cardiovascular disease; however the underlying mechanisms remain elusive. Disturbance of the endothelial glycocalyx (EG), an important regulator of vessel function, is thought to contribute to vascular pathology. Here, we studied the EG with respect to gestational and postnatal age in preterm and term neonates. The Perfused Boundary Region (PBR), an inverse measure of glycocalyx thickness, was measured postnatally in 85 term and 39 preterm neonates. Preterm neonates were further analyzed in two subgroups i.e., neonates born < 30 weeks gestational age (group A) and neonates born ≥ 30 weeks (group B). In preterm neonates, weekly follow-up measurements were performed if possible. PBR differed significantly between preterm and term neonates with lowest values representing largest EG dimension in extremely premature infants possibly reflecting its importance in fetal vascular development. Linear regression revealed a dependence of PBR on both, gestational age and postnatal age. Furthermore, hematocrit predicted longitudinal PBR changes. PBR measured in group A at a corrected age of > 30 weeks was significantly higher than in group B at birth, pointing towards an alteration of intrinsic maturational effects by extrinsic factors. These changes might contribute to the increased cardiovascular risk associated with extreme prematurity.


Assuntos
Doenças Cardiovasculares/diagnóstico por imagem , Diagnóstico por Imagem/métodos , Idade Gestacional , Glicocálix/química , Doenças do Prematuro/diagnóstico por imagem , Pele/diagnóstico por imagem , Doenças Cardiovasculares/metabolismo , Doenças Cardiovasculares/fisiopatologia , Estudos de Casos e Controles , Células Endoteliais/química , Células Endoteliais/patologia , Feminino , Glicocálix/patologia , Hematócrito , Humanos , Lactente , Recém-Nascido de Baixo Peso , Recém-Nascido , Recém-Nascido Prematuro , Doenças do Prematuro/metabolismo , Doenças do Prematuro/fisiopatologia , Modelos Lineares , Masculino , Estudos Prospectivos , Pele/irrigação sanguínea , Pele/metabolismo
16.
Int J Antimicrob Agents ; 58(4): 106405, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34289402

RESUMO

This work is dedicated to the memory of Hartmut Derendorf (1953-2020), a pioneer of modern pharmacokinetics and valued mentor of this project. OBJECTIVES: Septic infants/neonates need effective antibiotic exposure, but dosing recommendations are challenging as the pharmacokinetics in this age are highly variable. For vancomycin, which is used as a standard treatment, comprehensive pharmacokinetic knowledge especially at the infection site is lacking. Hence, an exploratory clinical study was conducted to assess the feasibility and safety of microdialysis sampling for vancomycin monitoring at the target site. METHODS: Nine infants/neonates with therapeutic indications for vancomycin treatment were administered 15 mg/kg as 1-hour infusions every 8-24 hours. Microdialysis catheters were implanted in the subcutaneous interstitial space fluid of the lateral thigh. Samples were collected every 30 minutes over 24 hours, followed by retrodialysis for catheter calibration. Prior in vitro investigations have evaluated impact factors on relative recovery and retrodialysis. RESULTS: In vitro investigations showed the applicability of microdialysis for vancomycin monitoring. Microdialysis sampling was well tolerated in all infants/neonates (23-255 days) without major bleeding or other adverse events. Pharmacokinetic profiles were obtained and showed plausible vancomycin concentration-time courses. CONCLUSIONS: Microdialysis as a minimally invasive technique for continuous longer-term sampling is feasible and safe in infants/neonates. Interstitial space fluid profiles were plausible and showed substantial interpatient variation. Hence, a larger microdialysis trial is warranted to further characterise the pharmacokinetics and variability of vancomycin at the target site and ultimately improve vancomycin dosing in these vulnerable patients.


Assuntos
Antibacterianos/sangue , Monitoramento de Medicamentos/métodos , Microdiálise/métodos , Vancomicina/sangue , Antibacterianos/administração & dosagem , Humanos , Recém-Nascido , Terapia Intensiva Neonatal/métodos , Microdiálise/efeitos adversos , Sepse/tratamento farmacológico , Sepse/microbiologia , Vancomicina/administração & dosagem
17.
BMJ Open ; 11(6): e050652, 2021 06 24.
Artigo em Inglês | MEDLINE | ID: mdl-34168035

RESUMO

PURPOSE: The MUNICH Preterm and Term Clinical (MUNICH-PreTCl) birth cohort was established to uncover pathological processes contributing to infant/childhood morbidity and mortality. We collected comprehensive medical information of healthy and sick newborns and their families, together with infant blood samples for proteomic analysis. MUNICH-PreTCl aims to identify mechanism-based biomarkers in infant health and disease to deliver more precise diagnostic and predictive information for disease prevention. We particularly focused on risk factors for pregnancy complications, family history of genetically influenced health conditions such as diabetes and paediatric long-term health-all to be further monitored and correlated with proteomics data in the future. PARTICIPANTS: Newborns and their parents were recruited from the Perinatal Center at the LMU University Hospital, Munich, between February 2017 and June 2019. Infants without congenital anomalies, delivered at 23-41 weeks of gestation, were eligible. FINDINGS: Findings to date concern the clinical data and extensive personal patient information. A total of 662 infants were recruited, 44% were female (36% in preterm, 46% in term). 90% of approached families agreed to participate. Neonates were grouped according to gestational age: extremely preterm (<28 weeks, N=28), very preterm (28 to <32 weeks, N=36), late preterm (32 to <37 weeks, N=97) and term infants (>37+0 weeks, N=501). We collected over 450 data points per child-parent set, (family history, demographics, pregnancy, birth and daily follow-ups throughout hospitalisation) and 841 blood samples longitudinally. The completion rates for medical examinations and blood samples were 100% and 95% for the questionnaire. FUTURE PLANS: The correlation of large clinical datasets with proteomic phenotypes, together with the use of medical registries, will enable future investigations aiming to decipher mechanisms of disorders in a systems biology perspective. TRIAL REGISTRATION NUMBER: DRKS (00024189); Pre-results.


Assuntos
Nascimento Prematuro , Proteômica , Estudos de Coortes , Feminino , Idade Gestacional , Hospitalização , Humanos , Recém-Nascido , Masculino , Morbidade , Gravidez , Nascimento Prematuro/epidemiologia
18.
J Pediatr ; 156(2): 191-6, 2010 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-19846115

RESUMO

OBJECTIVES: To assess potential effects of a hemodynamically significant persistent ductus arteriosus (sPDA) in the skin microcirculation in preterm neonates. STUDY DESIGN: In 25 patients (<32 weeks of gestation; birth weight <1250 g) with sPDA (n = 13) or no significant PDA (non-sPDA; n = 12) functional vessel density and vessel diameters were investigated prospectively. Sidestream dark field imaging was performed in the skin of both arms from the third day of life until PDA closure or until day 7 or 8 for the non-sPDA group. RESULTS: Before PDA treatment, functional vessel density was significantly lower in the sPDA group compared with the non-sPDA group. In the sPDA group, there were significantly fewer large vessels (diameter >20 microm) and significantly more small vessels (diameter <10 microm). After successful PDA treatment, these differences disappeared. In both groups, functional vessel density differed significantly between the left and right arm, persisting even after successful treatment. Regression analysis showed an inverse linear correlation between the hemodynamic echocardiographic findings and functional vessel density (P <.005). CONCLUSION: sPDA causes major changes in the microcirculation of premature neonates; functional vessel density is reduced, with a shift in perfusion from larger toward smaller vessels. The redistribution of flow might be a compensatory mechanism to preserve physiologic metabolism.


Assuntos
Permeabilidade do Canal Arterial/fisiopatologia , Recém-Nascido Prematuro , Pele/irrigação sanguínea , Permeabilidade do Canal Arterial/diagnóstico por imagem , Permeabilidade do Canal Arterial/cirurgia , Ecocardiografia , Hemodinâmica , Humanos , Recém-Nascido , Modelos Lineares , Microcirculação , Estudos Prospectivos , Resultado do Tratamento
19.
Environ Sci Technol ; 44(18): 7123-9, 2010 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-20722423

RESUMO

Perfluorinated compounds (PFCs) are a group of chemicals widely used for many applications. In this study PFCs were investigated in maternal blood during pregnancy (at two time points) (n = 40 and 38) and 6 months after delivery (n = 47), in cord blood (n = 33) and in blood of infants six (n = 40) and nineteen months (n = 24) after birth, and monthly in breast milk samples in Germany. Concentrations in maternal serum ranged from 0.5 to 9.4 µg/L for perfluorooctane sulfonate (PFOS) and 0.7 to 8.7 µg/L for perfluorooctanoic acid (PFOA). In cord serum, the values ranged from 0.3 to 2.8 µg/L and from 0.5 to 4.2 µg/L for PFOS and PFOA, respectively. The median results from serum at six and nineteen months of age were 3.0 and 1.9 µg/L for PFOS and 6.9 and 4.6 µg/L for PFOA, respectively. In breast milk samples, PFOS ranged from <0.03 to 0.11 µg/L (median: 0.04 µg/L), while PFOA was detected only in some samples as were all other PFCs. Overall, we found low levels of PFCs in cord sera and an increase in concentrations through the first months of infant life. Although the concentrations in breast milk were low, this intake led to a body burden at the age of six months similar to (PFOS) or higher than (PFOA) that found in adults.


Assuntos
Ácidos Alcanossulfônicos/sangue , Caprilatos/sangue , Monitoramento Ambiental , Fluorocarbonos/sangue , Efeitos Tardios da Exposição Pré-Natal/sangue , Adulto , Feminino , Sangue Fetal/metabolismo , Humanos , Fórmulas Infantis/química , Recém-Nascido , Leite Humano/química , Gravidez , Adulto Jovem
20.
BMJ Paediatr Open ; 4(1): e000740, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32984553

RESUMO

PURPOSE: The aim of this study was to assess morbidity and mortality pattern of small for gestational age (SGA) preterm infants in comparison to appropriate for gestational age (AGA) preterm infants of similar gestational age. METHOD: We compared neonatal outcomes of 1336, 1:1 matched, singleton SGA and AGA preterm infants based on their gestational age using data from the study 'Causes of Illness and Death of Preterm Infants in Ethiopia (SIP)'. Data were analysed using SPSS V.23. ORs and 95% CIs and χ2 tests were done, p value of <0.05 was considered statistically significant. RESULT: The majority of the infants (1194, 89%) were moderate to late preterm (32-36 weeks of gestation), 763 (57%) were females. Male preterm infants had higher risk of being SGA than female infants (p<0.001). SGA infants had increased risk of hypoglycaemic (OR and 95% CI 1.6 (1.2 to 2.0), necrotising enterocolitis (NEC) 2.3 (1.2 to 4.1), polycythaemia 3.0 (1.6 to 5.4), late-onset neonatal sepsis (LOS) 3.6 (1.1 to 10.9)) and prolonged hospitalisation 2.9 (2.0 to 4.2). The rates of respiratory distress syndrome (RDS), apnoea and mortality were similar in the SGA and AGA groups. CONCLUSION: Neonatal complications such as hypoglycaemic, NEC, LOS, polycythaemia and prolonged hospitalisation are more common in SGA infants, while rates of RDS and mortality are similar in SGA and AGA groups. Early recognition of SGA status, high index of suspicion and screening for complications associated and timely intervention to prevent complications need due consideration.

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